Magnetic Resonance Imaging Probes Research Articles

ChemInform Abstract: Design, Synthesis and Biological Application of Chemical Probes for Bio‐Imaging

AbstractReview: 29 refs.

PH-responsive polymeric micelle based on PEG-poly(β-amino ester)/(amido amine) as intelligent vehicle for magnetic resonance imaging in detection of cerebral ischemic area

A series of pH-responsive polymeric micelles is developed to act as intelligent carriers to deliver iron oxide (Fe 3O 4) nanoparticles and respond rapidly to an acidic stimuli environment for magnetic resonance imaging (MRI). The polymeric micelle can be self-assembled at physiological pH by a block copolymer, consisting of a hydrophilic methoxy poly(ethylene glycol) (PEG) and a pH-responsive poly(β-amino ester)/(amido amine) block. Consequently, the Fe 3O 4 nanoparticles can be well encapsulated into polymeric micelles due to the hydrophobic interaction, shielded by a PEG coronal shell. In an acidic environment, however, the pH-responsive component, which has ionizable tert-amino groups on its backbone, can become protonated to be soluble and release the hydrophobic Fe 3O 4 nanoparticles. The Fe 3O 4-loaded polymeric micelle was measured by dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and a 3.0 T MRI scanner. To assess the ability of this MRI probe as a pH-triggered agent, we utilize a disease rat model of cerebral ischemia that produces acidic tissue due to its pathologic condition. We found gradual accumulation of Fe 3O 4 nanoparticles in the brain ischemic area, indicating that the pH-triggered MRI probe may be effective for targeting the acidic environment and diagnostic imaging of pathologic tissue.

Magnetic Nanochains of FeNi3Prepared by a Template-Free Microwave-Hydrothermal Method

Magnetic FeNi3 nanochains were synthesized by reducing iron(III) acetylacetonate and nickel(II) acetylacetonate with hydrazine in ethylene glycol solution without any template under a rapid and economical microwave irradiation. The morphology and composition of the as-prepared products were characterized by field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and elemental mapping. The size of the aligned nanospheres in the magnetic FeNi3 chains could be adjusted from 150 to 550 nm by increasing the amounts of the precursors. The length of the nanochain is about several tens of micrometers. The ratio of the precursors plays an important role in the formation of FeNi3 nanostructures. Magnetic measurement reveals that the FeNi3 nanochains show enhanced coercivity and saturation magnetization. The formation mechanism of the product is discussed. Toxicity tests of FeNi3 nanochains show that the as-prepared nanochains are nontoxic to zebrafish larvae. In vitro magnetic resonance imaging (MRI) confirms the effectiveness of the FeNi3 nanochains as sensitive MRI probes.

Towards MRI contrast agents responsive to Ca(II) and Mg(II) ions: metal‐induced oligomerization of dota–bisphosphonate conjugates

In magnetic resonance imaging (MRI), paramagnetic complexes are utilized as contrast agents. Much attention has been paid to the development of new contrast agents responsive to pH, temperature or concentration of various components of body liquids. We report a new type of MRI probe sensing the concentrations of calcium and magnesium in biological media. The ligand do3ap(BP) combines a dota-like chelator with a bisphosphonate group. In the complex, the Gd(III) ion is entrapped in the macrocyclic cavity whereas the bisphosphonate group is not coordinated and therefore is available for coordination with endogenous metal ions. In the presence of metal ions, Gd-do3ap(BP) appears to show formation of coordination oligomers leading to an unprecedented increase in r(1) up to 200-500%. The extremely high relaxivity response makes this type of compound interesting for further studies as MRI ion-responsive probes for biomedical research.

In vivomolecular imaging using nanomaterials: Generalin vivocharacteristics of nano-sized reagents and applications for cancer diagnosis (Review)

Nanoparticles present a new collection of contrast agents for the field of in vivo molecular imaging. This review focuses on promising molecular imaging probes for optical and magnetic resonance imaging based on four representative nanomaterial(s) platforms: quantum dots, upconversion phosphors, superparamagnetic iron oxides, and dendrimer-based agents. Quantum dots are extremely efficient fluorescent nanoparticles with size-tunable emission properties, enabling high sensitivity and greater depth penetration. Their heavy metal composition and long retention in the body, however, pose concerns for clinical translational applications. Upconversion phosphors generate excellent signal-to-background contrast because they emit light with higher energy than the excitation photons and autofluorescence signals. For MRI, iron oxide particles also generate excellent signal and have been used in liver imaging and for cell tracking studies. As they are metabolized through endogenous iron salvage pathways, they have already been introduced as clinical contrast agents. Lastly, dendrimers, a 'soft' nanoparticle, can be used as a structural basis for the attachment of small molecule imaging agents and/or targeting groups. This array of nanoparticles should offer insights into the uses and potentials of nanoparticles for the molecular imaging.

Para-hydrogenated Glucose Derivatives as Potential 13C-Hyperpolarized Probes for Magnetic Resonance Imaging

A set of molecules in which a glucose moiety is bound to a hydrogenable synthon has been synthesized and evaluated for hydrogenation reactions and for the corresponding para-hydrogen-induced polarization (PHIP) effects, in order to select suitable candidates for an in vivo magnetic resonance imaging (MRI) method for the assessment of glucose cellular uptake. It has been found that amidic derivatives do not yield any polarization enhancement, probably due to singlet-triplet state mixing along the reaction pathway. In contrast, ester derivatives are hydrogenated in high yield and afford enhanced (1)H and (13)C NMR spectra after para-hydrogenation. The obtained PHIP patterns are discussed and explained on the basis of the calculated spin level populations in the para-hydrogenated products. These molecules may find interesting applications in (13)C MRI as hyperpolarized probes for assessing the activity of glucose transporters in cells.

Bone-Seeking Probes for Optical and Magnetic Resonance Imaging

In clinical practice the imaging of bone tissue is based almost exclusively on x-ray or radiochemical methods. Alternative methods, such as MRI and optical imaging, can provide not only anatomical, but also physiological information, due to their ability to reflect the properties of body fluids (temperature, pH and concentration of ions). In this article we review bone targeting probes for MRI and fluorescence imaging. As bone targeting is mainly associated with phosphonate and bisphosphonate derivatives, we also focus on their sorption behavior. Also discussed in detail is the limitation of using bone-targeting probes for MRI and optical imaging mainly due to their long-time retention in bone tissue and the low permeability of tissues for light.

Preparation of Uniform, Water‐Soluble, and Multifunctional Nanocomposites with Tunable Sizes

AbstractNovel, thiol‐functionalized, and superparamagnetic, silica composite nanospheres (SH‐SSCNs) with diameters smaller than 100 nm are successfully fabricated through the self‐assembly of Fe3O4 nanoparticles and polystyrene100‐block‐poly(acrylic acid)16 and a subsequent sol‐gel process. The size and magnetic properties of the SH‐SSCNs can be easily tuned by simply varying the initial concentrations of the magnetite nanoparticles in the oil phase. By incorporating fluorescent dye molecules into the silica network, the composite nanospheres can be further fluorescent‐functionalized. The toxicity of the SH‐SSCNs is evaluated by choosing three typical cell lines (HUVEC, RAW264.7, and A549) as model cells, and no toxic effects are observed. It is also demonstrated that SH‐SSCNs can be used as a new class of magnetic resonance imaging (MRI) probes, having a remarkably high spin–spin (T2) relaxivity (r2* = 176.1 mM−1 S−1). The combination of the sub‐100‐nm particle size, monodispersity in aqueous solution, superparamagnetism, and fluorescent properties of the SH‐SSCNs, as well as the non‐cytotoxicity in vitro, provides a novel and potential candidate for an earlier MRI diagnostic method of cancer.

Differentiation of Glioma and Radiation Injury in Rats Using In Vitro Produce Magnetically Labeled Cytotoxic T-Cells and MRI

BackgroundA limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models.Methodology/Principal FindingsCord blood T and CD14+ cells were collected. Isolated CD14+ cells were then converted to dendritic cells (DCs), primed with glioma cell lysate and used to sensitize T-cells. Phenotypical expression of the generated DCs were analyzed to determine the expression level of CD14, CD86, CD83 and HLA-DR. Cells positive for CD25, CD4, CD8 were determined in generated CTLs. Specificity of cytotoxicity of the generated CTLs was also determined by lactate dehydrogenase (LDH) release assay. Secondary proliferation capacity of magnetically labeled and unlabeled CTLs was also determined. Generated CTLs were magnetically labeled and intravenously injected into glioma bearing animals that underwent MRI on days 3 and 7 post- injection. CTLs were also administered to animals with focal radiation injury to determine whether these CTLs accumulated non-specifically to the injury sites. Multi-echo T2- and T2*-weighted images were acquired and R2 and R2* maps created. Our method produced functional, sensitized CTLs that specifically induced U251 cell death in vitro. Both labeled and unlabeled CTLs proliferated equally after the secondary stimulation. There were significantly higher CD25 positive cells (p = <0.006) in CTLs. In addition, T2- and T2*-weighted MR images showed increased low signal intensity areas in animals that received labeled CTLs as compared to the images from animals that received control cells. Histological analysis confirmed the presence of iron positive cells in sites corresponding to MRI low signal intensity regions. Significant differences (p = <0.001) in tumor R2 and R2* values were observed among the groups of animals. Animals with radiation injury exhibited neither MRI hypointense areas nor presence of iron positive cells.ConclusionOur results indicate that T-cells can be effectively sensitized by in vitro methods and used as cellular probes to identify and differentiate glioma from radiation necrosis.

Design, synthesis and biological application of chemical probes for bio-imaging

Biological imaging has revealed many new biological findings, among them GFP and other fluorescent proteins and small molecule based fluorescent probes have been widely used, especially in the past two decades. In this tutorial review the design concept and application of chemical probes are described-these are FRET based probes, Zn(2+) probes and MRI probes. Fluorescence resonance energy transfer (FRET) has been used extensively for the design principle for fluorescent probes. One of the most significant advantages of probes with FRET modulation is that these can enable ratiometric measurement in living cells, which reduces the artefacts from microscopic imaging systems. The design strategy for the development of a small molecular FRET probe is described, in terms of avoiding close contact between donor fluorophore and acceptor fluorophore in aqueous solution. Furthermore, a strategy to design a FRET probe with modulating overlap integral of donor and acceptor is introduced. Numerous tools for Zn(2+) sensing in living cells have become available in the last decade. Among them, fluorescence imaging using fluorescent probes has been the most popular approach. Some of these probes can be used to visualize Zn(2+) in living cells. Some of the biological functions of Zn(2+) were clarified using these probes, especially in neuronal cells, which contain a high concentration of free Zn(2+). Real-time imaging of enzyme activities in vivo offers valuable information in understanding living systems and in developing medicine for various types of diseases. Magnetic resonance imaging (MRI) is expected to be one of the most promising in vivo imaging techniques in the scientific and medical fields. One of the most promising nuclide for MRI is (19)F. (19)F atoms are concentrated in the form of solid salts mostly in bones and teeth in our bodies. The MRI signal of the intrinsic (19)F is hardly detectable. A novel design strategy for (19)F MRI probes in detecting protease activity is described.

Development of Responsive Lanthanide-Based Magnetic Resonance Imaging and Luminescent Probes for Biological Applications

Lanthanide complexes have unique chemical characteristics compared with typical organic complexes, and have recently attracted much interest because of the expanding need for new bioanalytical sensors. For example, magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging inside opaque organisms, and gadolinium ion (Gd(3+)) complexes have become important tools as MRI contrast agents. However, most of them are nonspecific, and report solely on anatomy. Therefore, responsive MRI contrast agents, so-called "smart" MRI contrast agents whose ability to relax water protons is greatly enhanced by recognition of a particular biomolecule, have great potential for elucidating biological phenomena. On the other hand, lanthanide complexes such as europium (Eu(3+)) and terbium (Tb(3+)) complexes have excellent luminescence properties for biological applications, i.e., long luminescence lifetime of the order of milliseconds and a large Stoke's shift of >200 nm. Their long-lived luminescence is especially suitable for time-resolved measurements, because the interference from short-lived background fluorescence and scattered light rapidly decays to a negligible level after a pulse of excitation light is applied, and the emitted light can be collected after an appropriate delay time. These luminescent lanthanide complexes have already found commercial use as highly sensitive luminescent probes in heterogeneous and homogeneous assays. This paper reviews our research on the design and synthesis of responsive lanthanide-based MRI and luminescent probes for advanced bioimaging.

Self-Assembly of SiO&lt;SUB&gt;2&lt;/SUB&gt;/Gd-DTPA-Polyethylenimine Nanocomposites as Magnetic Resonance Imaging Probes

Controlled self-assembly of organic/inorganic magnetic hybrid materials have important applications in magnetic resonance imaging (MRI). In this study, a widely used polycation polyethylenimine was conjugated with gadopentetic acid (Gd-DTPA) as a gadolinium bearing polyelectrolyte (Gd-DTPA-PEI). Next, multilayers of Gd-DTPA-PEI were coated on silica nanoparticles through layer-by-layer (LbL) self-assembly with polyanions as monitored by dynamic light scattering, zeta-potential, and scanning electron microscopy. The thickness of the multilayer film was estimated from quartz crystal microbalance based on counting frequency change of each adsorbed layer. The magnetic relaxation of SiO2/(Gd-DTPA-PEl/polyanion), core-shell nanocomposite was tested at 1.5 T magnetic field in a clinical MRI scanner, and a 3-fold increase in T1 relaxivity to 15.1 Gd mM(-1)s(-1) was noticed comparing to Gd-DTPA small molecules. Dextran sulfate was coated as the outermost layer on the nanocomposite for better biocompatibility as verified by in vitro cytotoxicity studies. This formulation provides good signal intensity enhancement of mouse liver in vivo with only 1/25 dose of clinical standard at 30 and 60 minutes after intravenous injection. This sensitive imaging probe with unique core-shell structures may find broad applications in cellular and molecular imaging.

Interest of Diffusion Weighted Magnetic Resonance Imaging for the Evaluation of Bone Marrow Infiltration in Multiple Myeloma, Smoldering Myeloma and Monoclonal Gammopathy of Undetermined Significance.

Abstract 4874 IntroductionMonoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM) are two asymptomatic early stages of multiple myeloma, and are characterized by the absence of bone involvement. In contrast, bone lytic lesions are common complications of multiple myeloma. Magnetic resonance imaging (MRI) has improved the evaluation of bone involvement in multiple myeloma. Moreover MRI allows visualization of the medullary cavity and a direct assessment of the degree of myeloma cell infiltration before bone destruction becomes visible on plain radiographs. Diffusion weighted magnetic resonance imaging (DWI) probes the diffusion of water in the body. This sequence yields qualitative and quantitative information that reflects the tissue cellularity and cell membrane intregrity and thus complements morphological information obtained by conventional MRI. It shows considerable promise for detecting and characterizing tumors and evaluating treatment response. ObjectiveOur objective was to study the potential interest of diffusion weighted MRI for the evaluation of bone marrow infiltration in multiple myeloma, SMM and MGUS. Diagnostic criteria used were those defined by the International Myeloma Working Group. Patients and methodsThis retrospective study was conducted over a period of 8 months (November 2008 - June 2009) in Internal Medicine and Hematology departments of our institution. All patients who had a whole body MRI for evaluation of multiple myeloma, SMM or MGUS were included. We choose to study simultaneously 3 complementary sequences: T1 weighted, short time inversion recovery (STIR) and diffusion weighted. ResultsSeventy patients were included in this study: 9 MGUS, 19 SMM and 42 symptomatic multiple myeloma (16 at diagnosis and 27 at relapse). They were 30 men and 40 women. The median age was 64 years (36 - 89 years). Thirty one of the 42 multiple myeloma patients have focal bone lesions. Focal lesions were observed in the 3 MRI sequences and diffusion did not detect new lesions. Regarding bone marrow infiltration assessment by MRI, four groups of patients could be identified: - Group 1 (20 patients – 28.6%): normal signal in T1, STIR, and diffusion. - Group 2 (19 patients – 27.1%): abnormal signal involving the whole spine on the STIR or diffusion weighted sequences and with a normal signal of the spine on T1.- Group 3 (25 patients – 35.7%): abnormal signal involving the whole spine on the STIR and diffusion weighted sequences and with a normal signal of the spine on T1.- Group 4 (6 patients – 8.6%): abnormal signal involving the whole spine on the 3 sequences. For the 28 patients with either MGUS or SMM, the distribution in the 4 groups was respectively 13 patients (46.4%), 7 patients (25.0%), 7 patients (25.0%) and 1 patient (3.6%) for group 1,2 3 and 4. Regarding the 42 cases of symptomatic multiple myeloma, 7 patients (16.7%) were classified in group 1, 12 (28.6%) in group 2, 18 (42.9%) in group 3 and 5 (11.9%) in group 4. There was no correlation between number of focal lesions and degree of diffuse infiltration. The degree of bone marrow infiltration evaluated by MRI was not correlated with Durie and Salmon stage, ISS, monoclonal component concentration or bone marrow plasmocytosis. DiscussionDiffusion weighted magnetic resonance imaging combined with conventional sequences (T1 and STIR) can distinguish 4 groups of patients with different aspects of bone marrow infiltration. Fifteen patients (53.6%) with either MGUS or SMM had various degree of bone marrow infiltration without any focal lesions. A prospective study on a large population of MGUS and SMM is needed to assess the impact of these asymptomatic infiltrations on the risk of malignant transformation. The degree of bone marrow infiltration evaluated by MRI is very heterogeneous between patients with multiple myeloma and not correlated with classical prognostic factors. Further prospective studies are necessary to investigate the possible prognostic impact of these different groups on the evolution of myeloma. DisclosuresNo relevant conflicts of interest to declare.

Bioresponsive nanosensors in medical imaging

Superparamagnetic iron oxide nanoparticles have been established as sensitive probes for magnetic resonance imaging (MRI). While the majority of specific nanosensors are based on sterically stabilized iron oxide particles, the focus of this review is on the use of very small iron oxide particles (VSOPs) that are electrostatically stabilized by an anionic citrate acid shell. We used VSOPs to develop target-specific as well as protease-activatable nanosensors for molecular MRI.

Amphiphilic dextran/magnetite nanocomposites as magnetic resonance imaging probes

Superparamagnetic iron oxide (SPIO) nanoparticles are effective contrast agents for enhancement of magnetic resonance imaging at the tissue, cellular or even molecular levels. High quality SPIO nanoparticles can be synthesized in the organic phase but need to be transferred into water before any biomedical applications. In this study, amphiphilic poly(e-caprolactone) grafted dextran (Dex-g-PCL) was used as carriers for particle encapsulation and stabilization in the aqueous phase. Multiple SPIO nanoparticles were self-assembled together with the help of Dex-g-PCL during phase transfer from chloroform to water, and diameters of Dex-g-PCL/SPIO nanocomposites were (64 ± 22) nm through dynamic light scattering measurement. These nanocomposites were superparamagnetic at 300 K with saturated magnetization of 88 emu/g Fe. In the magnetic field of 1.5 T, Dex-g-PCL/SPIO nanocomposites had a T2 relaxivity of 363 Fe mL·mol−1·s−1. This unique nanocomposite brought significant mouse liver contrast with signal intensity changes of −60% at 5 min after intravenous administration. However, uptake of Dex-g-PCL/SPIO nanocomposites in liver reticuloendothelial cells (Kupffer cells) did not immediately happen at shorter time points (〈4 h) as verified by histology studies, and it was evident that more iron staining would be located in Kupffer cells 24 h after contrast agent administration. After 24 h and 10 d, the signal intensities (SI) gradually recovered, and SI changes were −44% and −31%, respectively. From our observation, the time window for enhanced-MRI could last at least 12 days and totally recovered after 16 days. This novel sensitive MRI contrast agent may find potential applications in discovering small liver lesions such as early tumor diagnosis.

New vanadium-based magnetic resonance imaging probes: clinical potential for early detection of cancer

We have developed a magnetic resonance imaging (MRI) method for improved detection of cancer with a new class of cancer-specific contrast agents, containing vanadyl (VO(2+))-chelated organic ligands, specifically bis(acetylacetonato)oxovanadium(IV) [VO(acac)(2)]. Vanadyl compounds have been found to accumulate within cells, where they interact with intracellular glycolytic enzymes. Aggressive cancers are metabolically active and highly glycolytic; an MRI contrast agent that enters cells with high glycolytic activity could provide high-resolution functional images of tumor boundaries and internal structure, which cannot be achieved by conventional contrast agents. The present work demonstrates properties of VO(acac)(2) that may give it excellent specificity for cancer detection. A high dose of VO(acac)(2) did not cause any acute or short-term adverse reactions in murine subjects. Calorimetry and spectrofluorometric methods demonstrate that VO(acac)(2) is a blood pool agent that binds to serum albumin with a dissociation constant K (d) ~ 2.5 +/- 0.7 x 10(-7) M and a binding stoichiometry n = 1.03 +/- 0.04. Owing to its prolonged blood half-life and selective leakage from hyperpermeable tumor vasculature, a low dose of VO(acac)(2) (0.15 mmol/kg) selectively enhanced in vivo magnetic resonance images of tumors, providing high-resolution images of their interior structure. The kinetics of uptake and washout are consistent with the hypothesis that VO(acac)(2) preferentially accumulates in cancer cells. Although VO(acac)(2) has a lower relaxivity than gadolinium-based MRI contrast agents, its specificity for highly glycolytic cells may lead to an innovative approach to cancer detection since it has the potential to produce MRI contrast agents that are nontoxic and highly sensitive to cancer metabolism.

Catheter-based flexible microcoil RF detectors for internal magnetic resonance imaging

Flexible catheter probes for magnetic resonance imaging (MRI) of the bile duct are demonstrated. The probes consist of a cytology brush modified to accept a resonant RF detector based on a spiral microcoil and hybrid integrated capacitors, and are designed for insertion into the duct via a non-magnetic endoscope during endoscopic retrograde cholangiopancreatography (ERCP). The coil must be narrow enough (<3 mm) to pass through the biopsy channel of the endoscope and sufficiently flexible to turn through 90° to enter the duct. Coils are fabricated as multi-turn electroplated conductors on a flexible base, and two designs formed on SU-8 and polyimide substrates are compared. It is shown that careful control of thermal load is used to obtain useable mechanical properties from SU-8, and that polyimide/SU-8 composites offer improved mechanical reliability. Good electrical performance is demonstrated and sub-millimetre resolution is obtained in 1H MRI experiments at 1.5 T magnetic field strength using test phantoms and in vitro liver tissue.

Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells

The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [β-Ala11, Phe13, Nle14]bombesin-(7-14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.

AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

BackgroundDespite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan.ResultsThree million human breast cancer (MDA-MB-231) cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro) complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT) images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro) complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor) was significantly different between animals that received non-transduced and transduced cells (P < 0.001).ConclusionThis study indicates that genetically transformed, magnetically labeled APCs can be used both as delivery vehicles and cellular probes for detecting in vivo migration and homing of cells. Furthermore, they can potentially be used as a gene carrier system for the treatment of tumor or other diseases.

Nanoparticle Enhanced Imaging

Nanotechnology refers to the research and technical development of objects in a scale range of 1 to 100 nanometers. Particles that are nano-sized are opening new research avenues in the field of engineering and life sciences. Imaging with biocompatible nanoparticles has emerged as one of the most promising new diagnostic imaging technology fulfilling the goal of developing cost-effective magnetic nanoparticles with acceptable targeting efficiency, favorable pharmacokinetics and a good safety profile. These nanoparticles target the reticuloendothelial system and this combined with unique properties of superparamagnetism allows them to be used as excellent probes for magnetic resonance imaging (MRI). The current issue focusses on the use of a specific type of magnetic nanoparticle (ferumoxtran10) to overcome imaging handicaps in cancer staging as well as discuss emerging applications of newer magnetic nanoparticles. Imaging with ferumoxtran-10 offers the potential of staging tumors at stages much earlier that those detectable today. Therapy decisions and prognostic predictions for most tumors depend on the accurate lymph node staging at the time of initial diagnosis. Despite the importance of nodal status, accurate staging of lymph nodes in various primary tumors continues to pose a major diagnostic challenge. Following the detection of lymph nodes, the next arduous task is the characterization of nodes into benign and malignant categories. Current cross-sectional modalities like CT and MRI primarily rely on nodal size and nodal morphology for differen-